Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene.
In mice lacking the nociceptin (or orphanin FQ) receptor gene, when 10 mg/kg of morphine was subcutaneously given, a potent analgesia in the tail pinch test was observed. The analgesic effect of morphine was equivalent among wild-type, heterozygous and homozygous mutant mice. When morphine was given to such mice in a dose of 10 mg/kg once per day for 5 days, wild-type and heterozygous mice showed marked tolerance or reduction in the morphine analgesia on the 5th day, while homozygous mice showed only 50% reduction in the peripheral analgesia of morphine. These findings suggest that nociceptin or its receptor plays important roles in the in vivo mechanism for the development of morphine tolerance.
Ueda
H
H
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Japan. ueda@net.nagasaki-u.ac.jp
Yamaguchi
T
T
Tokuyama
S
S
Inoue
M
M
Nishi
M
M
Takeshima
H
H
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D004361:Drug Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009154:Mutation; D010147:Pain Measurement / Q000187:drug effects; D011957:Receptors, Opioid / Q000235:genetics*; D000094942:Nociceptin Receptor
D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D009020:Morphine; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse